title: Therapeutic effect of lecithinized superoxide dismutase against colitis.
abstract: Ulcerative colitis (UC) involves intestinal mucosal damage induced by reactive oxygen species (ROS), in particular, superoxide anion. Superoxide dismutase (SOD) catalyzes dismutation of superoxide anion to hydrogen peroxide, which is subsequently detoxified by catalase. Lecithinized SOD (PC-SOD) is a new modified form of SOD that has overcome previous clinical limitations of SOD. In this study, we examined the action of PC-SOD using an animal model of UC, dextran sulfate sodium (DSS)-induced colitis. DSS-induced colitis was ameliorated by daily intravenous administration of PC-SOD. Unmodified SOD produced a similar effect but only at more than 30 times the concentration of PC-SOD. In vivo electron spin resonance analysis confirmed that the increase in the colonic level of ROS associated with development of colitis was suppressed by PC-SOD administration. The dose-response profile of PC-SOD was bell-shaped, but simultaneous administration of catalase restored the ameliorative effect at high doses of PC-SOD. Accumulation of hydrogen peroxide was observed with the administration of high doses of PC-SOD, an effect that was suppressed by the simultaneous administration of catalase. We also found that either a weekly intravenous administration or daily oral administration of PC-SOD conferred protection. These results suggest that PC-SOD achieves its ameliorative effect against colitis through decreasing the colonic level of ROS and that its ineffectiveness at higher doses is because of the accumulation of hydrogen peroxide. Furthermore, we consider that intermittent or oral administration of PC-SOD can be applied clinically to improve the quality of life of UC patients.
authors.affiliation: Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ishihara
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tasaka
authors.forename: Takushi
authors.initials: T
authors.lastname: Namba
authors.forename: Jun
authors.initials: J
authors.lastname: Suzuki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishihara
authors.forename: Susumu
authors.initials: S
authors.lastname: Okamoto
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Takenaga
authors.forename: Rie
authors.initials: R
authors.lastname: Igarashi
authors.forename: Keizo
authors.initials: K
authors.lastname: Sato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mizushima
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000818:Animals; D002374:Catalase / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics; D053759:Interleukin-23 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D010713:Phosphatidylcholines / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000627:therapeutic use*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D007375:Interleukin-1; D053759:Interleukin-23; D015850:Interleukin-6; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase